Stimulation of calcium-sensing receptors induces endothelium-dependent vasorelaxations via nitric oxide production and activation of IKCa channels

Vascular Pharmacology
Harry Z E GreenbergAnthony P Albert

Abstract

Stimulation of vascular calcium-sensing receptors (CaSRs) is reported to induce both constrictions and relaxations. However, cellular mechanisms involved in these responses remain unclear. The present study investigates the effect of stimulating CaSRs on vascular contractility and focuses on the role of the endothelium, nitric oxide (NO) and K(+) channels in these responses. In wire myography studies, increasing [Ca(2+)]o from 1mM to 6mM induced concentration-dependent relaxations of methoxamine pre-contracted rabbit mesenteric arteries. [Ca(2+)]o-induced relaxations were dependent on a functional endothelium, and were inhibited by the negative allosteric CaSR modulator Calhex-231. [Ca(2+)]o-induced relaxations were reduced by inhibitors of endothelial NO synthase, guanylate cyclase, and protein kinase G. CaSR activation also induced NO production in freshly isolated endothelial cells (ECs) in experiments using the fluorescent NO indicator DAF-FM. Pre-treatment with inhibitors of large (BKCa) and intermediate (IKCa) Ca(2+)-activated K(+) channels (iberiotoxin and charybdotoxin), and Kv7 channels (linopirdine) also reduced [Ca(2+)]o-induced vasorelaxations. Increasing [Ca(2+)]o also activated IKCa currents in perforated-patch re...Continue Reading

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Citations

Mar 28, 2018·International Journal of Molecular Sciences·Andrea Gerbino, Matilde Colella
Jun 29, 2018·Neurocritical Care·Mostafa JafariAfshin A Divani
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Apr 4, 2021·International Journal of Molecular Sciences·Sai Sahana Sundararaman, Emiel P C van der Vorst

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Methods Mentioned

BETA
fluorescence microscopy

Software Mentioned

MicroCal Origin
GraphPad
EqCal
AxioVision
Graphpad Prism
pCLAMP
Zeiss LSM 510
MicroCal
LSM 510

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